The nature of the chemical alterations in the human epileptic cortex were investigated further using in vitro slice techniques and autoradiography. The in vitro slices, and the addition of norepinephrine, glutamate, NMDA, and somatostatin were used individually or in combination in order to determine whether the epileptic focus had a different responsiveness at the level of cyclic nucleotides and inositol phosphate. The responsiveness of the epileptic tissue under in vitro conditions was not significantly different from the surrounding less epileptic tissue. PET scan studies have indicated that the binding of the mu opiod receptor was slightly elevated in the spiking epileptic cortex when compared to the nonspiking cortex. To investigate this finding further, sections of the spiking and nonspiking epileptic cortex were exposed to [3-H]-DAGO, a selective mu opiate receptor ligand, and adjacent sections to [3-H)-DADLE, a mu and delta receptor ligand. The major findings of the study are that there are no significant differences for the number of receptor sites or their affinity in the spiking versus nonspiking cortex. The distribution of the mu and delta receptors was observed to be different. In the spiking and nonspiking cortex, the mu receptors were in a heterogeneous manner with the peak layers found in two bands at 1/3 and 1/2 the distance between the meninges and the white matter. In the same tissues, the delta receptor was homogeneously distributed but did have a gradient with the highest number of receptors located in the outermost layer of the cortex. The number of TCP receptors in the spiking versus nonspiking cortex was also investigated using [3-H]-TCP. The findings were that there were no receptor number or affinity changes when the spiking and nonspiking tissues were compared. The distribution of TCP receptors was similar in the two tissues and had a gradient with the highest number of receptors localized in the outermost layers of the cortex.